Tubulin, the dimeric protein of microtubules, exists as various isoforms in different tissues and species. Tubulin is the target protein for various antitumor drugs such as paclitaxel, vinbiastine and vincristine, which are routinely used for cancer chemotherapy. Previous studies from this laboratory have shown that certain tubulin isoform exhibit preferential interaction with antitumor drugs. Thus, the isoform composition of a tissue may affect the antimitotic properties of any drug. Here, breast cancer cells were tested for the presence of different tubulin isoforms by immunoblotting and RT-PCR analysis. Breast cancer cells were made resistant to antitumor drugs paclitaxel and podophyllotoxin and the tubulin isoform content was studied. The results show that paclitaxel-resistant MCF-7 cells had 2-3 fold increase in Pu and Pu' expression than that of the wild type. On the other hand, podophyllotoxin- resistant MDA-MB-23 1 cells had an increased expression of P% than that of the wild type cells. A full length cDNA for P',, was prepared. This cDNA will be used to construct a plasmid for the overexpression of P,i, tubulin in the breast cancer cells. The cells will be tested for the sensitivity to antitumor drugs. These results will be very important for proper selection as well as design of novel drugs for breast cancer.